The Brazilian
Cystic Fibrosis Patient Registry
2014
The Brazilian
Cystic Fibrosis Patient Registry
2014
2014 ANNUAL REPORT To all the people interested in cystic fibrosis: The Brazilian Cystic Fibrosis Patient Registry (REBRAFC) contains demographic data on the diagnosis and treatment of patients with cystic fibrosis (CF) in Brazil, which is aimed at improving attention to the disease in our country. This is the sixth year the report has been published, with increasing participation of colleagues and centers operating in Brazil. There is still much to do for Brazilian patients, who lack access to diagnostic and therapeutic resources in various regions of the country. The continuity and solidity of REBRAFC is of particular importance in this scenario, as it is the main documented feature of the real situation of Brazilian patients and their evolution over the years, showing, therefore, how CF is being diagnosed and treated in the country. We believe that this initiative can contribute to changes in the government’s agenda and result in better health care for individuals with CF in Brazil.
About Cystic Fibrosis and The Brazilian Cystic Fibrosis Study Group.: Cystic fibrosis (CF) is an autosomal recessive disease with multisystemic involvement (respiratory, gastrointestinal, hepatic, and genitourinary systems). It is a complex, progressive, and potentially lethal disease but still scarcely known in Brazil, despite the existence of some specialized centers and professionals dedicated to studying it and taking care of patients for many years. Treatment is also complex and involves high-cost medications, of which some are funded by the Ministry of Health and others are funded by the State Health Departments, so access to medicines is not uniform in the country. The Brazilian Cystic Fibrosis Study Groups (GBEFC) is a nonprofit organization composed of healthcare professionals working in the area, established on November 5, 2003. Among the activities of the GBEFC are the dissemination of research, staff training and aiding in the development of CF treatment centers in the country, organizing scientific meetings about the disease (five editions of the Brazilian CF Congress), working with the Ministry of Health for defining a national protocol of CF care, and implementation of newborn screening in the remaining Brazilian states. The GBEFC maintains an Internet site (www.gbefc.org.br) that provides information on cystic fibrosis. This report and previous ones (2009, 2010, 2011, 2012, and 2013) are available for free download in Portuguese and English versions.
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The Brazilian
Cystic Fibrosis Patient Registry
2014
EXECUTIVE COMMITTEE OF THE BRAZILIAN CYSTIC FIBROSIS REGISTRY: Dr. Luiz Vicente Ribeiro Ferreira da Silva Filho • Executive Coordinatorof the REBRAFC • Assistant Professor at the Pediatric Pulmonology Unit, Instituto da Criança (HCFMUSP) • Researcher at the Research and Learning Institute of Hospital Israelita Albert Einstein, São Paulo, SP
Dr. Francisco José Caldeira Reis • • • •
Former Presidentof the Brazilian Cystic Fibrosis Study Group Professor of Pediatrics at the Federal University of Minas Gerais (UFMG) Pediatric Pulmonologist trained at Prof. Victor Chernick’s Service, University of Manitoba, Children’s Hospital of Winnipeg, Manitoba, Canada Advisor of the Hospital Infantil João Paulo II, Rede FHEMIG, Belo Horizonte, MG
Prof. Dr. Paulo José Cauduro Maróstica • Full Professor, Department of Pediatrics, UFRGS • Coordinator of the GP in Health of Children and Adolescents, UFRGS • Head of the Pediatric Pulmonology Unit, Hospital de Clínicas de Porto Alegre, RS
Dr. Rodrigo Abensur Athanazio • Assistant Physician of the Pulmonology Department at the Instituto do Coração (InCor) of Hospital das Clínicas da FMUSP
Dra. Neiva Damaceno • Assistant Professor at the Pediatric Pulmonology Group of the Faculty of Medical Sciences of Santa Casa de São Paulo • Former Presidentof the Brazilian Cystic Fibrosis Study Group (GBEFC)
Adilson Yuuji Hira • Engineer • Laboratory of Integrated Systems, Escola Politécnica of the University of São Paulo (USP)
Angela Tavares Paes
• Statistician Federal University of São Paulo (UNIFESP) • Doctorate from the Institute of Mathematics and Statistics, University of São Paulo (IME-USP) • Applied Statistics Sector, Pro-Rectory of Graduate Studies and Research, Federal University of São Paulo
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The Brazilian
Cystic Fibrosis
REBRAFC Highlights in 2014
Patient Registry
4
2014
1
A total of 3,511 patients were registered, of whom 3,327 (94.7%) had some annual follow-up data (some spirometry and/or anthropometry data).
2
More than 50% of patients already had at least 3 years of follow-up (2,043 patients, 58.2%).
3
In the country, 166 new cases were diagnosed, and newborn screening accounted for about 70% of new diagnoses. The median age of diagnosis of the patients, however, is still 1.19 years.
4
The median age of Brazilian patients was 11.5 years, and about 25% of patients were 18 years or older.
5
Brazil still had 5 to 10 >10 to 15 >15 to 20 >20 to 25 >25 to 30 >30 to 35 >35 to 40 >40 to 45 >45 to 50 >50 years Total of patients Patients with no information
N (%) 666 (21.0%) 709 (22.4%) 676 (21.4%) 512 (16.2%) 230 (7.3%) 135 (4.3%) 75 (2.4%) 55 (1.7%) 35 (1.1%) 21 (0.7%) 52 (1.6%) 3,166 (100%) 216
Age group (pediatric – adult) A R334W R1162X G85E N1303K W1282X S4X S549R 3849+10kbC>T R1066C R553X 2183AA>G G551D 1717-1G>A 711+1G>T Y1092X 1078delT 1812-1G>A D1152H I507del L206W P205S S549N 3272-26A>G 2789+5G>A A561E R347P
Frequency
% according to the total of alleles
1523 139 38 36 32 31 26 16 12 11 11 9 9 8 8 7 6 6 5 5 5 4 4 3 3 3 2 2 2
47.48% 4.33% 1.18% 1.12% 1.00% 0.97% 0.81% 0.50% 0.37% 0.34% 0.34% 0.28% 0.28% 0.25% 0.25% 0.22% 0.19% 0.19% 0.16% 0.16% 0.16% 0.12% 0.12% 0.09% 0.09% 0.09% 0.06% 0.06% 0.06%
Mutation 2789+5G>A 3659delC M1101K R1158X R75Q 1341+1G>A 1898+1G>A 2184delA 2184insA 3121-1G>A 3132delTG 711+1G>T 711+5G>A 991del5 A559T c.2051-2052del AAinsG 4382delA G576A D579G E585X 2307insA L997F 2347delG Q220X R347P R347H R851X W1089X
Frequency
% according to the total of alleles
2 2 2 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
0.06% 0.06% 0.06% 0.06% 0.06% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03% 0.03%
OBS: The table lists only the mutations recorded in the CFTR2 database, excluding non-pathogenic polymorphisms or dependent on combinations with pathogenic mutations to result in protein dysfunction.
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The Brazilian
Cystic Fibrosis Patient Registry
2014
FOLLOW-UP DATA For describing the follow-up data, only the year 2014 was considered (n = 2,571).
5. ANTHROPOMETRIC DATA Anthropometric data were obtained on the day of the pulmonary function test or the last visit of the year, in situations in which the pulmonary function test was not performed. In the calculations of the percentiles and Z scores of the anthropometric data, the data from the Centers for Disease Control and Prevention (CDC), USA (available in http://www.cdc.gov/growthcharts/), were used as reference.
Table14
Description of the patients according to anthropometric data. WEIGHT (kg) Mean (standard deviation) Median (p25;p75) Total number of patients
BMI (kg/m2) Mean Median (p25;p75) Total number of patients
NCHS percentile
Z score
33.96 (29.80) 26.00 (7;56) 1,968
-0.68 (1.26) -0.63 (-1.47; 0.15) 1,968
HEIGHT (cm) Mean (standard deviation) Median (p25, p75) Total number of patients
Absolute Value
NCHS percentile
Z score
33.94 (28.87) 26.00 (8; 55) 1,967
-0.63 (1.15) -0.63 (-1.38; 0.13) 1,967
NCHS percentile
(18-year-old patients or older)
(patients younger than 18 years old)
21.33 (3.74) 20.80 (18.80;23.23) 568
43.42 (32.06) 41.00 (13; 71) 1,377 p25, 25th percentile; p75, 75th percentile.
By analyzing the nutritional parameters according to age, the percentiles and Z scores of the anthropometric measures tended to decrease over the years in patients younger than 18 years (Figures 13 and 14). The strong association between nutrition and disease severity is evidenced by the worsening of nutritional parameters and pulmonary function (see below). On the other hand, in the adult patients, BMI tended to increase with age (Figure 15). This finding may result from a survival bias in the adult population, as patients with more-severe disease progress to premature death and the remaining patients have milder disease and better nutritional status, with a higher concentration of atypical cases.
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The Brazilian
Cystic Fibrosis Patient Registry
2014
Figure 13
Evolution of the median percentiles of weight, height, and BMI from (20 to 50 years years), 2014. 70%
Median percentile
60% 50% 40% 30% 20% 10% 0%
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
16
17
18
Age (years) BMI median percentile
Weight median percentile
Height median percentile
Figure 14
Evolution of weight and height Z scores according to age (from 2 to 18 years), 2014. 0.00
Z score mean
-0.20 -0.40 -0.60 -0.80 -1.00 -1.20
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Age (years) Weight Z score mean
Height Z score mean
Figure 15
Evolution of body mass index (BMI) according to age (from 2 to 18 years), 2014. Median BMI (kg/m2)
31.0 29.0 27.0 25.0 23.0 21.0 19.0 17.0 15.0
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50
Age (years) 18
The Brazilian
Cystic Fibrosis Patient Registry
2014
6. PULMONARY FUNCTION DATA Spirometry data are available for 1,322 patients (51.4%). For patients with more than one functional test in the year, the test data with the best values for pulmonary function were inserted. For the predicted values of pulmonary function, the publication by Stanojevic et al, Spirometry Centile Charts for Young Caucasian Children: The Asthma UK Collaborative Initiative. American Journal of Respiratory and Critical Care Medicine 2009, 180(6); 547552, was used as a reference. Table 15
Description of the patients according to pulmonary function data. Z score – FVC Mean (standard deviation) Median (p25, p75) Total number of patients
FEV1-predicted Percentage -1.54 (2.09) -1.33 (-2.94; -0.16) 1,307
82.21 (24.09) 84.28 (65.90; 98.18) 1,307
Z score – FEV1 Mean (standard deviation) Median (p25, p75) Total number of patients
-2.13 (2.17) -1.91 (-3.92; -0.51) 1,307
FEV1/FVC
FVC Predicted Percentage Mean (standard deviation) Median (p25, p75) Total number of patients
Mean (standard deviation) Median (p25, p75) Total number of patients
Mean (standard deviation) Median (p25, p75) Total number of patients
73.49 (27.27) 76.73 (52.06; 94.07) 1,307
Z score – FEV1/FVC 0.76 (0.14) 0.79 (0.67; -0.87) 1,319
Mean (standard deviation) Median (p25, p75) Total number of patients
-1.37 (1.63) -1.35 (-2.65; -0.24) 1,307
n=number of patients; p25, 25th percentile; p75, 75th percentile; FVC, forced vital capacity; FEV1, forced expiratory volume.
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2014
The Brazilian
Cystic Fibrosis Patient Registry
In the analysis of the data of pulmonary function according to age, forced expiratory volume (FEV1) values showed a progressive and sharp decrease with age, less evidently after 20 years old. Figure 16
FEV1-predicted percentage according to age (from 6 to 30 years old), 2014. 120 110 100
FEV1-predicted percentage
90 80 70 60 50 40 30 20 10
Sex Female Male
0 6
8
10
12
14
16
18
20
22
24
26
28
30
Age at spirometry (years)
These data can also be observed in Table 19 and Figure 17, which examine the distribution of patients according to age and degree of obstruction. A significant proportion of children and adolescents with functional changes already established. In the statistical analysis (chi-square test), a strong association was found between the degree of obstruction and age group (p < 0.001), demonstrating a progressive functional loss. Table 16
Degree of obstruction according to age group, 2014. Age group Degree of obstruction Normal (predicted FEV1 % ≥ 90%) Normal/mild (predicted FEV1 % ≥ 70% and 30 Years
Total
Mild (%VEF1 predito >=40% e < 70%)
Severe (predicted FEV1 % < 40%)
Age group Normal (predicted FEV1 % ≥ 90%)
Mild (predicted FEV1 % ≥ 70% and < 90%)
By analyzing the evolution of pulmonary function over the years (2009–2014), we observed that the FEV1 and FVC values remain relatively unchanged over the period studied, with slight increases in the last year (Figure 18). Figure 18
Variations in the percentages of the FVC- and FEV1-predicted values from 2009 to 2014. 84 82
81.77
82.52
81.93
81.58
81.67
72.55
72.39
2012
2013
82.21
Predicted percentage mean
80 78 76 74
73.30 72.74
73.28
73.50
72 70 68 66
2009
2010
2011 Predicted FEV1 %
2014
Predicted FVC %
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2014
The Brazilian
Cystic Fibrosis Patient Registry
Among the factors potentially associated with worsening of pulmonary function, nutrient levels and pulmonary function showed a relationship, both in pediatric patients (BMI percentile × FEV1 values) and adults (BMI × FEV1 value; Figures 19 and 20). Figure 19
Figure 20
120
100
FEV1-predicted percentage according to BMI percentile in the patients aged 6 to 18 years, 2014.
FEV1-predicted percentage according to BMI in patients aged 20 to 40 years old, 2014. 90 80
FEV1-predicted percentage
FEV1-predicted percentage
100
80
60
40
20 Ideal (50th percentile)
70 60 50 40 30 20 10
0
0 0
10
20
30
40
50
60
70
80
90
100
10
12
BMI percentile
Female Male
22
16
18
20
22
BMI(kg/m2) Sex
Sex
14
Female Male
24
26
28
30
The Brazilian
Cystic Fibrosis Patient Registry
2014
7. MICROBIOLOGIC DATA Microbiological data refer to the identification of the pathogen in question at least once a year. As the processing techniques and culture of respiratory samples from patients with cystic fibrosis patients in Brazil have not been standardized yet, the data must be interpreted with caution. Table 17
Description of the microorganisms identified. Microorganisms identified Oxacillin-sensitive Staphylococcus aureus Pseudomonas aeruginosa Non-mucoid Pseudomonas aeruginosa Mucoid Pseudomonas aeruginosa
Burkholderia cepacia complex Haemophilus influenzae Oxacillin-resistant Staphylococcus aureus Stenotrophomonas maltophilia Klebsiella pneumoniae Candida species Achromobacter species Serratia species Aspergillus fumigatus Escherichia coli Other Pseudomonas Mycobacterium non-tuberculosis Mycobacterium tuberculosis Total number of patients
n
%
1,505 1,081 712 524 231 229 215 112 137 137 77 73 68 66 43 12 1 2,571
58.5% 42.0% 27.7% 20.4% 9.0% 8.9% 8.4% 4.4% 5.3% 5.3% 3.0% 2.8% 2.6% 2.6% 1.7% 0.5% 0.04% 100%
Similarly to the mode observed in previous reports and international data, in the early years of life, a prevalence of colonization by oxacillin-sensitive Staphylococcus aureus is observed, gradually diminishing during adolescence (Table 18 and Figure 21). In parallel, there is a progressive increase in the identification of Pseudomonas aeruginosa, and this pathogen becomes the most frequent in the adult age group. The prevalence of oxacillin-resistant Staphylococcus aureus also increases over the years. It is interesting to notice the reduction in the identification of Burkholderia cepacia complex from the age of 35 years, which may represent the survival bias in milder cases, with a higher proportion of atypical forms of CF. Table 18
Microorganisms identified according to age group. Microorganisms identified Age group (years) Up to 5 > 5 to 10 >10 to 15 >15 to 20 >20 to 25 >25 to 30 >30 to 35 >35 years
Oxacillin-sensitive Pseudomonas Haemophilus Burkholderia cepacia Oxacillin-resistant S. aureus aeruginosa influenzae complex S. aureus 58.2% 35.6% 11.8% 6.8% 7.5% 69.3% 36.4% 11.4% 9.7% 7.4% 64.1% 42.5% 10.4% 9.7% 10.2% 57.9% 46.3% 7.2% 9.1% 9.1% 43.9% 54.4% 4.7% 9.9% 8.2% 48.2% 61.8% 0.9% 12.7% 11.8% 50.0% 63.8% 0.0% 13.8% 12.1% 32.4% 45.4% 1.9% 8.3% 4.6%
Stenotrophomonas maltophilia 4.8% 4.0% 6.5% 3.3% 4.1% 0.9% 3.4% 2.8%
n* 584 580 537 361 171 110 58 108
*Total: 2,509 patients (62 patients with no information about age))
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2014
The Brazilian
Cystic Fibrosis Patient Registry
Figure 21
Prevalence of pathogens identified according to age group. 70%
53%
35%
18%
0%
Up to 5 years
> 5 to 10
>10 to 15
Oxacillin-sensitive S. aureus Oxacillin-resistant S. aureus
>15 to 20
>20 to 25
>25 to 30
Pseudomonas aeruginosa Haemophilus influenzae
>30 to 35
>35 years
Burkholderia cepacia complex Stenotrophomonas maltophilia
Figure 22
Percentage of patients with Pseudomonas aeruginosa from 2009 to 2014. 49.9%
50.0%
50% 45.5%
42.5%
44.0%
42.0%
38% 31.6% 27.2% 25%
20.4% 21.8%
22.6%
2011
2012
21.4%
13%
0% 2009
2010
% of patients with mucoid pseudomonas
24
2013
% of patients with pseudomonas
2014
2014
The Brazilian
Cystic Fibrosis Patient Registry
8. CLINICAL TREATMENT DATA A total of 11,368 medical appointments were made in 2014, with a median of 4 medical appointments per patient/year. Figure 23
Distribution of the patients according to the number of medical appointments performed in 2014.
Frequency
600
400
200
0
1
2
3
4
5
6
7
8
9
10
11
12
13
Number of medical appointments
14
15
16
17
18
21
Table 19
Deaths. Deaths
n (%)
No Yes
2525 (98.2%) 46 (1.8%)
Causes of death* Respiratory failure Septic shock/sepsis
31 8
Unknown origin – 6 Abdominal septic shock (enterocolitis) – 1 Septicemia due to piercing – 1
Hemorrhagic shock (after lung transplantation) Hypovolemic shock (dehydration) Hematemesis Acute myocardial infarction Femur osteosarcoma Unknown Total of patients Age at death (years) Mean (standard deviation) Median (p25–p75) Minimum–maximum
19.80 (10.15) 18.98 (14.21-25.65) 0.27-41.64
2 1 1 1 1 1 2,571 (100%) Observation: In this report and in the previous ones, the percentage of deaths was calculated considering only the total of patients followed in the reference year. This estimate does not represent the survival of patients. It is worth highlighting that the most appropriate analysis of the deaths is the one using median survival curves.
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The Brazilian
Cystic Fibrosis Patient Registry
2014
Table 20
Shwachman-Kulczycki score: total score according to age group (up to 18 years, n = 1,636). Age group Total score Severe (≤40) Moderate (41–55) Mild (56–70) Good (71–85) Excellent (86–100) Total of patients
Up to 5 years 9 (1.8%) 17 (3.5%) 48 (9.8%) 157 (32.1%) 258 (52.8%) 489 (100%)
> 5 to 10 9 (1.9%) 23 (4.8%) 60 (12.4%) 197 (40.7%) 194 (40.1%) 483 (100%)
>10 to 15 25 (5.4%) 56 (12.1%) 90 (19.4%) 178 (38.4%) 114 (24.6%) 463 (100%)
>15 to 18 12 (6.0%) 29 (14.4%) 49 (24.4%) 79 (39.3%) 32 (15.9%) 201 (100%)
Total 55 (3.4%) 125 (7.6%) 247 (15.1%) 611 (37.3%) 598 (36.6%) 1,636 (100%)
Figure 24
Confidence intervals (95%) for the mean Shwachman-Kulczycki scores according to age group (up to 18 years, n = 1,636).
Shwachman score (95% CI)
85.00
80.00
75.00
70.00
Up to 5 years
> 5 to 10
> 10 to 15
Age group
26
> 15 to 18
The Brazilian
Cystic Fibrosis Patient Registry
2014
Table 21
Complications/comorbidities in the last year. Complications/comorbidities in the last year Asthma Evidence of liver involvement Gastroesophageal reflux disease Diabetes Nasal polyposis Osteopenia/osteoporosis Hemoptysis Chronic atelectasis Pulmonary hypertension Cirrhosis with portal hypertension Cholelithiasis Allergic bronchopulmonary aspergillosis Distal intestinal obstruction syndrome Pancreatitis Pneumothorax Hematemesis Intestinal invagination Colonic stenosis Total number of patients
n (%) 305 (11.9%) 226 (8.8%) 145 (5.6%) 123 (4.8%) 122 (4.7%) 107 (4.2%) 89 (3.5%) 49 (1.9%) 32 (1.2%) 26 (1.0%) 25 (1.0%) 22 (0.9%) 17 (0.7%) 13 (0.5%) 9 (0.4%) 6 (0.2%) 3 (0.1%) 1 (0.04%) 2,571 (100%) n=number of patients.
Table 22
Transplants. Transplants Lung transplant – corpse donor Liver transplant Total number of patients
n (%) 24 (0.9%) 1 (0.04%) 2,571 (100%)
Table 25
Inhalants. Bronchodilators Short-acting beta 2 agonist Long-acting beta 2 agonist Anticholinergic Antibiotics Inhalant tobramycin 300 mg Colomycin Amikacin Gentamicin Injectable tobramycin Vancomycin Aztreonam Others Mucolytics Alfadornase N-Acetylcysteine Salines 0.9% saline 3% hypertonic saline 5% hypertonic saline 7% hypertonic saline Total number of patients
n (%) 848 (33.0%) 543 (21.1%) 94 (3.7%) n (%) 1,001 (38.9%) 432 (16.8%) 24 (0.9%) 11 (0.4%) 16 (0.6%) 8 (0.3%) 4 (0.2%) 47 (1.8%) n (%) 1,846 (71.8%) 100 (3.9%) n (%) 455 (17.7%) 107 (4.2%) 117 (4.6%) 508 (19.8%) 2,571 (100%) n=number of patients
Table 23
Oxygen therapy. Oxygen therapy No Yes Continuous Nocturnal Total of patients
n (%) 2,479 (96.4%) 92 (3.6%) 43 (1.7%) 49 (1.9%) 2,571 (100%)
Table 24
Insulin Use of insulin No Yes Total number of patients
n (%) 2,457 (95.6%) 114 (4.4%) 2,571 (100%) 27
The Brazilian
Cystic Fibrosis Patient Registry
2014
Table 26
Table 28
Oral medicines
Intravenous treatments: hospitalizations.
Pancreatic enzymes
n (%)
Intravenous treatments
n (%)
2,073 (80.6%)
Home care* Hospital care* Home and hospital care Total Total number of patients
72 (12.4%) 484 (83.3%) 25 (4.3%) 581 (22.6%) 2,571 (100%)
10,000 U/kg/day
180 (8.7%)
Unknown
20 (1.0%)
Nutritional supplements
1,636 (63.6%)
Oral
*Percentage in relation to the total number of patients in treatment
1,487 (90.9%)
Gastrostomy
61 (3.7%)
Cycles/year
Gastric tube
19 (1.2%)
Unknown
69 (4.2%)
Mean (standard deviation) Median (p25–p75) Total number of patients
Azithromycin Proton pump inhibitors Ursodeoxycholic acid Corticosteroid H2 blockers Ibuprofen or other NSAIDs (arthropathy) Ibuprofen (pulmonary disease) Total number of patients
960 (37.3%) 609 (23.7%) 504 (19.6%) 184 (7.2%) 176 (6.8%) 11 (0.4%) 6 (0.2%) 2,571 (100%)
n=number of patients. *The percentages regarding the enzyme doses or type of supplement were calculated based on the subgroup(s) that used enzymes/supplements.
Table 27
Pseudomonas aeruginosa eradication treatment P. aeruginosa eradication treatment Yes No Unknown Total number of patients
1.74 (1.22) 1 (1-2) 570
Days/patient/year Mean (standard deviation) Median (p25–p75) Total number of patients
26.04 (22.25) 15 (14-28) 572
Catheter implanted
n (%)
No Yes Total number of patients
2,534 (98.6%) 37 (1.4%) 2,571 (100%)
n (%) 583 (22.7%) 1.223 (47.6%) 765 (29.8%) 2,571 (100%)
Table 29
Intravenous antibiotics: days of hospitalization per year according to age group. Age group Days/year Mean (SD) Median (p25–p75) Total number of patients
28
Up to 5 years 21.7 (30.1) 14 (14-21) 129
> 5 to 10 22.0 (18.3) 14 (14-28) 86
>10 to 15 26.2 (22.9) 15 (14-28) 127
>15 to 20 28.4 (24.0) 19.5 (14-35) 104
>20 years 29.1 (28.1) 20.0 (14-34) 114
Total 26.2 (25.5) 15 (14-29) 560
The Brazilian
Cystic Fibrosis Patient Registry
2014
Table 30
Intravenous antibiotics: drugs used Drugs used Ceftazidime Amikacin Oxacillin Imipenem/meropenem Ciprofloxacin Sulfa-Trimethoprim Tobramycin Vancomycin Piperacillin/tazobactam Cefepime Gentamicin Linezolid Colomycin Cefuroxime Ticarcillin/piperacillin Aztreonam Chloramphenicol Others Total number of patients
n
(%)
358 345 190 140 121 107 89 77 59 59 25 18 12 12 8 8 1 47 2,571
13.9% 13.4% 7.4% 5.4% 4.7% 4.2% 3.5% 3.0% 2.3% 2.3% 1.0% 0.7% 0.5% 0.5% 0.3% 0.3% 0.04% 1.8% 100% n=number of patients.
Table 31
Specific data of the adult population. Sex Azoospermia/hypospermia* Pregnancy Oral or injectable contraceptive Stable union Job Total number of patients aged ≥18 years
Male 39 (12.8%) 45 (14.8%) 108 (35.5%) 304
Female 9 (3.4%) 42 (15.7%) 85 (31.7%) 82 (30.6%) 268
Total 39 9 42 130 (22.7%) 190 (33.2%) 572 *Patients reporting investigation
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The Brazilian
Cystic Fibrosis Patient Registry
2014
9. SURVIVAL This is the first year we published our survival analysis where we used the available follow-up data. Deaths due to other causes (femur osteosarcoma, septicemia due to piercing, accidental death, unknown cause, acute myocardial infarction, and car accident) were excluded. The same methodology used by the American organization Cystic Fibrosis Foundation (CFF) was adopted, using the same statistical analysis program. It should be noted that the survival curves only decreased in the ages at which deaths were observed. Given the small number of deaths registered in our platform, the curves of the Brazilian data show more apparent declines than the curves of the CFF, which has a substantially continuous decrease. Between 2010 and 2014, 115 deaths by cystic fibrosis were recorded. Figure 26 shows the survival curve that considers all the patients observed in this period.
Figure 25
Survival curve by the Cox method: total number of patients from 2010 to 2014. 1 0.9
Estimated survival probability
0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0
0
10
20
30
40
50
60
Age (years) 95% CI lower limit
Estimated survival
95% CI higher limit
From the curve, an estimate of the median survival age, which is the age at which the survival rate (or estimated survival probability) reaches 50%, can be obtained. However, as the volume of Brazilian data is much smaller and the total follow-up time was still relatively short, the median survival estimate has poor accuracy. By observing the data obtained in this analysis, we found that the median survival was between 41.7 and 54.9 years, with a lower limit of 37.7 years (age when the confidence interval crosses the line of the 50% survival probability).
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The Brazilian
Cystic Fibrosis Patient Registry
2014
Acknowledgments: This work would not be possible without the support of the pharmaceutical companies listed below, which ethically sponsored the initiative with enthusiasm, even without any perspective of privileged access to data or availability of marketing actions in the document.
• Novartis Biociências S. A. • Abbott Laboratórios do Brasil Ltda. • Zambon Laboratórios Farmacêuticos Ltda. • Multicare Pharmaceuticals • Produtos Roche Químicos e Farmacêuticos S. A. We also thank all health-care professionals involved in the care of the patients with cystic fibrosis for their cooperation in this initiative, which we believe will bring great benefits to patients with cystic fibrosis in our country.
31
The Brazilian
Cystic Fibrosis Patient Registry
2014
Centers that contributed to this report by providing the patients’ follow-up data in 2014 (in alphabetical order for states): Hospital
32
City
State
Responsible
Hospital Universitário Prof. Alberto Antunes – UFAL
Maceió
AL
Katharina Vidal de Medeiros Moura
Hospital Especializado Otavio Mangabeira
Salvador
BA
Maria Angélica Santana
Hospital Universitário Prof. Edgar Santos
Salvador
BA
Edna Lúcia Santos de Souza
Hospital Infantil Albert Sabin
Fortaleza
CE
Cláudia de Castro e Silva
Hospital da Criança de Brasília José Alencar
Brasília
DF
Luciana de Freitas Velloso Monte
Hospital de Base do Distrito Federal
Brasília
DF
Clarice Guimarães de Freitas
Hospital Infantil Nossa Senhora da Glória
Vitória
ES
Roberta de Cássia Melotti
Hospital Dr Dório Silva
Vitória
ES
Daniele Menezes Torres
Hospital das Clínicas da UFGO
Goiânia
GO
Lusmaia Damaceno Camargo Costa
APAE Anápolis
Anápolis
GO
Eliane Pereira dos Santos
Hospital Universitário Materno-Infantil de São Luis
São Luis
MA
Dra Denise Haidar
Hospital Infantil João Paulo II
Belo Horizonte
MG
Alberto Andrade Vergara
Hospital das Clínicas da UFMG
Belo Horizonte
MG
Dra Elizabet Vilar
Consultorio Francisco Reis
Belo Horizonte
MG
Francisco José Caldeira Reis
Hospital Julia Kubitschek
Belo Horizonte
MG
Marcelo de Fuccio
Hospital Universitário da UFJF
Juiz de Fora
MG
Marta Cristina Duarte
Hospital das Clinicas da UFMG - adultos
Belo Horizonte
MG
Marina Nishi
Hospital Universitario Maria Aparecida Pedrossian
Campo Grande
MS
Valéria Cristina de Ruchkys
Hospital Universitário João de Barros Barreto
Pará
PA
Valéria de Carvalho Martins
Hospital Universitario Lauro Wanderley
João Pessoa
PB
Constantino Cartaxo
Instituto Materno Infantil de Pernambuco
Recife
PE
Murilo Carlos Amorim de Britto
Hospital Pequeno Príncipe
Curitiba
PR
Paulo Kussek
The Brazilian
Cystic Fibrosis Patient Registry
2014
Hospital
City
State
Responsible
Hospital das Clínicas da UFPR
Curitiba
PR
Carlos Antônio Riedi
Hospital das Clinicas da UFPR - Adultos
Curitiba
PR
Mariane Martynychen
Instituto Fernandes Figueira
Rio de Janeiro
RJ
Tania Wrobel Folescu
Hospital Universitário Pedro Ernesto - UERJ
Rio de Janeiro
RJ
Agnaldo J. Lopes
Hospital de Pediatria da Universidade do Rio Grande do Norte
Natal
RN
Vera Maria Dantas
Hospital de Clínicas de Porto Alegre - UFRGS
Porto Alegre
RS
Paulo Cauduro Maróstica
Hospital de Clínicas de Porto Alegre - Adultos
Porto Alegre
RS
Paulo de Tarso Roth Dalcin
Hospital São Lucas - PUCRS
Porto Alegre
RS
Leonardo Araújo Pinto
Santa Casa de Porto Alegre
Porto Alegre
RS
Gilberto Bueno Fischer
Hospital Santa Isabel
Blumenau
SC
Glaunir Maria Foletto
Hospital Infantil Joana de Gusmão
Florianópolis
SC
Norberto Ludwig Neto
Hospital Infantil Jeser Amarante Faria
Joinville
SC
Tiago Neves Veras e Rafaela C. Benvenutti da Costa
Hospital das Clínicas da UNESP
Botucatu
SP
Giesela Fleischer Ferrari
Hospital das Clínicas da UNICAMP (pediatria)
Campinas
SP
Antonio Fernando Ribeiro
Hospital das Clínicas da USP Ribeirão Preto
Ribeirão Preto
SP
Lidia Alice Gomes M. M. Torres
Hospital de Base Fac Med de SJ Rio Preto
São José do Rio Preto
SP
Katia Izabel de Oliveira
Irmandade da Santa Casa de Misericórdia de São Paulo
São Paulo
SP
Neiva Damaceno
Instituto da Criança do Hospital das Clínicas da FMUSP
São Paulo
SP
Joaquim Carlos Rodrigues
Hospital da UNIFESP
São Paulo
SP
Sonia Mayumi Chiba
Hospital das Clínicas da FMUSP
São Paulo
SP
Rafael Stelmach
Consultorio Fabiola Adde
São Paulo
SP
Fabíola Vilac Adde
Centro de Puericultura - CPAP
São Paulo
SP
Luiz Vicente Ribeiro F. da Silva Filho
33
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